Laser-directed microcavitation is a photomechanical interaction involving the generation of vapor bubbles within a medium possessing a liquid phase, upon absorption of pulsed laser energy by the medium. The medium can be homogeneous comprising only the liquid phase, or can be heterogeneous and comprises the liquid phase mixed with one or more solid phases. For laser pulse durations shorter than a few microseconds, microcavitation can be a dominant mechanism causing alterations of the medium in which it is taking place. As laser energy is absorbed by the medium, the medium temperature rises at a rate that depends on the characteristics of both the medium and the laser beam. Above a certain threshold temperature, vaporization of the medium occurs and one or several vapor bubbles starts to expand. During bubble expansion, the vapor cools down and the bubble's internal pressure decreases. At some moment during the process, the bubble's internal pressure is no longer sufficient to overcome the external pressure, and a maximum bubble volume is reached as the expansion stops. A contraction phase follows, after which the bubble disappears. Following the first expansion-collapse cycle, additional oscillations with decreasing maximum bubble volumes can be observed.
In general, the total volume of medium potentially altered by laser-directed microcavitation is determined by two principal contributions. A first contribution involves thermally-induced effects, for which the affected volume is determined by the diffusion of heat within the medium as a result of the absorption of laser energy. A second contribution includes mechanically-induced alterations originating from stresses developing in the medium as the microcavitation bubbles expand and collapse. In the latter case, the mechanically-affected volume of medium around the bubble's center is at least as large as the maximum volume of the cavitation bubble.
An example of a heterogeneous medium is the cytoplasm of cells, particularly pigmented cells where the pigments absorb the energy. Selective Retina Therapy (SRT) is an example of an application which may involve or exploit laser-directed microcavitation. The absorption of laser light by melanin pigments synthetized in the melanosomes, which are membrane-bound organelles of the Retinal Pigment Epithelium (RPE) cells, can be exploited to selectively alter these cells. For such applications, it is often critical and difficult to predict and control the total volume of medium affected thermally and photomechanically. Currently, documented work examining the influence of time-domain irradiation parameters on the spatial extent of thermal and photomechanical alterations produced by microcavitation has mainly focused on the impact of the laser pulse duration. For example, it is well-known that as the pulse duration is reduced, the threshold radiant exposure to initiate microcavitation is also reduced because of improved thermal confinement (R. Brinkmann et al., “Selective RPE photodestruction: mechanism of cell damage by pulsed-laser irradiance in the ns to μs time regime”, Proc. SPIE 3601, Laser-Tissue Interaction X: Photochemical, Photothermal, and Photomechanical, (Jun. 14, 1999)). As the pulse duration becomes short compared to the characteristic heat diffusion time within the medium, steeper temperature gradients can be locally produced because heat has less time to diffuse away during exposure to the pulse. The critical temperature for bubble formation can thus be reached with less energy delivered to the medium, because less energy escapes from the absorption centers present in the medium during exposure to the pulse. Short pulses are therefore more attractive than long pulses from a purely thermal point of view, because microcavitation can be triggered with lower energy levels of laser energy and with better spatial confinement of the thermally-induced alterations.
On the other hand, it is also well-known that as the pulse duration is shortened, the vaporization tends to become more explosive (J. Neumann and R. Brinkmann, “Microbubble dynamics around laser heated microparticles”, in Therapeutic Laser Applications and Laser-Tissue Interactions, R. Steiner, ed., Proc. SPIE 5142, paper 5142_82 (Oct. 17, 2003)). With shorter pulses, the maximum bubble volume increases more rapidly with radiant exposure, making the control of the bubble volume more challenging. Therefore, the benefit of using shorter pulses from a thermal perspective can be cancelled by the risk of losing control over the volume of medium altered photomechanically. As a consequence, trade-offs involving longer pulse durations have been so far necessary to mitigate this risk, which lead to sacrifices on the thermal confinement.
A closer look at the distribution of melanosomes inside RPE cells is instructive for understanding the importance of controlling cavitation bubbles and heat diffusion in SRT procedures. As illustrated in FIG. 1 (PRIOR ART), melanosomes tend to gather on the apical side of RPE, close to the RPE-photoreceptor interface, and the distance between individual melanosomes and the photoreceptors can be as small as 1 μm or even in the sub-micron range. As heat typically diffuses at a rate of roughly 1 μm per μs in the retina, pulses longer than 1 μs are likely to induce thermal damages to the fragile photoreceptors. Currently, SRT procedures rely on Q-switch laser pulses having a duration of about 1.7 μs, mainly because shorter pulse durations are considered too dangerous due to the lack of control on the volume of the cavitation bubbles. For Q-switch pulses having a duration of 1.8 μs, a self-limitation phenomenon of the cavitation bubble size upon increase of the radiant exposure above the cavitation threshold has been reported in microcavitation experiments carried out with suspensions of porcine melanosomes in water (J. Neumann and R. Brinkmann, “Microbubble dynamics around laser heated microparticles”, in Therapeutic Laser Applications and Laser-Tissue Interactions, R. Steiner, ed., Proc. SPIE 5142, paper 5142_82 (Oct. 17, 2003)). These experiments showed that short Q-switch pulses (e.g. 12 ns duration) produce a rapid increase of the average bubble size with radiant exposure, whereas for longer Q-switch pulses (e.g. 1.8 μs) the bubble size remains essentially constant and small over a certain range of radiant exposures (FIG. 2).
A constant bubble volume would be beneficial from a clinical perspective since bubbles of limited volume can be produced without a strong dependency over the radiant exposure, which represents a practical advantage for the clinicians in the context of variable eye transmission and pigmentation levels from patient to patient.
Overall, current techniques of microcavitation are limited for controlling both types of confinement at the same time. In applications, this translates into a limited precision for creating specific, local alterations of the medium. This lack of spatial resolution can lead to detrimental effects, as a consequence of collateral alterations created at locations that were not initially targeted. There is therefore a need for improving precision in such applications of laser-directed microcavitation.